Altered autoantigen structure in Sjögren's syndrome: Implications for the pathogenesis of autoimmune tissue damage

Research output: Contribution to journalReview article

Abstract

The etiology and pathogenic mechanisms underlying Sjögren's syndrome (SS) remain unclear. Recent studies have emphasized that the specific autoantibodies that occur in a high proportion of patients with SS may provide important insights into the circumstances that initiate and propagate tissue damage in this disease. Although autoantigens targeted in systemic autoimmune diseases share little in common in terms of structure, subcellular distribution, or function in normal cells, these molecules are unified by becoming clustered and concentrated in the surface blebs of apoptotic cells. Furthermore, their structure is altered during some types of cell death to generate structures not previously generated during development and homeostasis. This review highlights the susceptibility of SS autoantigens to undergoing such structural changes during activation of immune effector pathways, and synthesizes a model of SS incorporating these concepts. An understanding of the mechanisms responsible for activating the specific immune response in SS, and the role of specific immune effector pathways in propagating both the autoimmune response and tissue damage, is of potential therapeutic importance. Abbreviations used in this paper are: CTL, cytotoxic T-lymphocytes; ER, endoplasmic reticulum; GluR3, subunit III of the glutamate receptor; GrB, granzyme B; M3R, type III muscarinic receptor; NK cells, natural killer cells; PARP, poly(ADP-ribose)polymerase; SS, Sjögren's syndrome; SLE, systemic lupus erythematosus; and UV, ultraviolet.

Original languageEnglish (US)
Pages (from-to)156-164
Number of pages9
JournalCritical Reviews in Oral Biology and Medicine
Volume15
Issue number3
DOIs
StatePublished - Dec 1 2004

Keywords

  • Apoptosis
  • Autoantibody
  • Autoantigen
  • Autoimmunity
  • Caspase
  • Granzyme B
  • Protease
  • Structure

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Dentistry(all)

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